PLATINUM ANALOG COMBINATION CHEMOTHERAPY - CISPLATIN, CARBOPLATIN, AND METHOTREXATE IN PATIENTS WITH METASTATIC UROTHELIAL TRACT TUMORS - APHASE-II TRIAL WITH EVALUATION OF PROGNOSTIC FACTORS

Background. Cisplatin is one of the single drugs that has shown the be st documented effect in treating patients with locally recurrent or me tastatic urothelial cancer. To the authors' knowledge, the effect of t he combination of different platinum analogues in treating transitiona l cell carcinoma has not been evaluated previously neither experimenta lly nor in clinical studies. Methods. A Phase II trial of carboplatin (200 mg/m(2)), cisplatin (100 mg/m(2)), and methotrexate (250 mg/m(2)) with folinic acid rescue every 3 weeks was performed on 55 previously untreated patients with metastatic or locally recurrent urothelial ce ll carcinoma. Results. A response (complete response and partial respo nse) was achieved in 21 of 51 evaluable patients (41%; 95% confidence limits, 28-56%). Twelve patients had no change, whereas 18 had progres sive disease. Eight patients (16%) achieved a complete response, and m ost of these survived more than 2 years. No patient with poor performa nce (performance status score greater than or equal to 2) or bone meta stases achieved a complete response. The median survival for all patie nts was 8.4 months. Multivariate survival analyses showed that perform ance status and alkaline phosphatase levels were significant prognosti c factors for survival. Conclusion. Combination therapy with cisplatin , carboplatin, and methotrexate is feasible but offers no advantage ov er other combinations with cisplatin and methotrexate in treating meta static urothelial cell cancer. It is important to select patients for treatment carefully, and further studies of prognostic factors in thes e patients are warranted.